The overall objective of the program is the development of novel compounds that exhibit biological activity of interest in the treatment of AIDS. The specific aims of the program are: (i) The development of efficient and innovative chemistry for the synthesis of modified sugars related to ribose and deoxyribose. (ii) The utilization of these modified sugars in the synthesis of novel nucleoside analog as potential anti-AIDS drugs. (ii) To increase the understanding of the relationship between structure and biological activity in nucleoside analog which exhibit such activity by functioning as reverse transcriptase inhibitors and/or chain terminators during viral DNA synthesis. In some cases the syntheses will begin with common sugars or their derivatives such as diacetone glucose, in other cases the starting material will be cyclopentadiene and the syntheses will incorporate enzymatic asymmetrizations of meso derivatives. Many of the novel compounds proposed are derivatives of branched-chain sugars with methyl, trifluoroethyl and other alkyl groups strategically placed. Methods for the production of 4-C-alkyl ribose derivatives, especially 4-C-methyl and 4-C-trifluoroethyl derivatives are stressed. Application of trifluoroethyl-trimethylsilane for the introduction of trifluoroethyl groups in appropriate carbohydrate derivatives will be explored. Nucleoside derivatives of the ribo, 2-deoxyribo- and 2,3-dideoxyribo classes will be prepared and submitted for screening.